This is a proposal to study the electrophysiologic properties of a chloride-secreting epithelium - the dog trachea. The role of selective permeabilities of the apical and basal membranes in regulating chloride secretion will be studied by changes in conductances in response to agents that inhibit or stimulate secretion and to changes in ion composition of the bathing solutions. An important element will be measurement of intracellular chloride activity and its repsonse to secretory changes, in order to test the major hypothesis of this secretion, that active chloride uptake occurs as a coupled NaC1 flux at the serosal membrane, with passive downhill efflux at the mucosal membrane. Regulation of flux will also be studied by monitoring of intracellular sodium and calcium activities with newly developed ion-selective microelectrodes. The ultimate goal is both understanding of the basic cellular mechanism of chloride secretion and insight into the pathophysiology of secretory defects in cystic fibrosis.